There is a fundamental gap in our understanding of host and organism precursors to the emergence of vancomycin-resistant Staphylococcus aureus (VRSA), a major public health concern. This career development award will support the further training of Emily Martin, MPH PhD, as she investigates the epidemiology and outcomes of a key precursor to VRSA emergence: dual infection due to methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The award will further Dr. Martin's long-term goal to evolve our understanding of the interrelated factors that drive the spread of antibiotic-resistant infections in the general population. The overall objective of this applicatio is to establish an independent research program to determine the risk factors and outcomes of patients with dual infection with MRSA and VRE as well as the specific molecular characteristics and strain types of the infecting organisms. We propose the following Specific Aims: (1) To identify the key clinical and demographic risk factors for infection with both MRSA and VRE; (2) To define the risk of post-infection adverse outcomes including length of stay following culture in patients with acute dual infections due to both MRSA and VRE compared to patients with infections due to MRSA or VRE alone; (3) To determine the risk factors for infection with hypersusceptible MRSA strains and/or MRSA or VRE containing molecular elements which facilitate the transfer of resistance between bacterial species. A notable strength of this study s that it will be performed in Southeast Michigan, the area with the highest prevalence of VRSA in the world, with the support of expert mentors (Drs. Keith Kaye and Michael Rybak) and excellent training in topics specific to bacterial infection. The expected outcomes are: 1) to identify key risk factors that will serve as a foundation for future prevention studies; 2) to collct detailed, prospective data on patient out- comes, which will identify opportunities to improve care; and 3) to identify a target population most at risk of VRSA infection through characterization of molecular elements that drive the emergence of vancomycin resistance in clinical VRE and MRSA isolates. The proposed research is relevant to public health because of the urgent need to better understand precursors to the emergence of vancomycin-resistant S. aureus (VRSA), particularly in the Detroit metro area. This epidemiologic study of the risk factors, characteristics, and outcomes of dual infections with MRSA and VRE is a key step in understanding and ultimately preventing future emergence of vancomycin resistance. This research is relevant to the mission of the NIAID in that it will have a positive impact on the futue prevention of antimicrobial resistance in two high-priority organisms and on the identification of key patient groups for intervention. This research will lead to improvement of outcomes in patients of interest throughout the NIH, including elderly populations and individuals with chronic disease, by examining the interaction between host factors, molecular determinants of resistance, and polymicrobial infections.